Alterations in .alpha..sub.1 -adrenergic receptors have far reaching physiological effects and drugs which selectively interact with .alpha..sub.1 -adrenergic receptors have an array of therapeutic applications. For example, .alpha..sub.1 -adrenergic receptor antagonists are useful in treating various cardiovascular disorders. .alpha..sub.1 -Adrenergic receptor antagonists block .alpha. receptors that mediate vasoconstriction in resistance arterioles and are useful as antihypertensive agents or as afterload reducing agents in treating congestive heart failure. Certain .alpha..sub.1 -adrenergic receptor antagonists can selectively reduce vascular resistance in specific organs (Blue, D.; Vimont, R.; Clarke, D. Br. J. Pharmacol. 1992, 107, 414-417) and are useful in treating ischemia of vital organs caused by, or associated with, persistent hypovolemic or cardiogenic shock or diabetic nephropathy. In addition, .alpha..sub.1 -adrenergic receptor stimulation contributes to arrhythmogenesis in the ischemic heart (Kurz, T.; Yamada, A.; DaTorre, S.; Corr, P. Eur. Heart J. 1991, 12, 88-98); thus, .alpha..sub.1 -adrenergic receptor antagonists are useful as antiarrhythmic agents.
.alpha..sub.1 -Adrenergic receptor antagonists are useful in treating various urinary tract disorders (Lepor, H. The Prostate Supplement. 1990, 3, 75-84). .alpha..sub.1 -Adrenergic receptor antagonists can selectively inhibit .alpha..sub.1 receptor mediated contraction of urethral and bladder neck smooth muscle, leading to decreased resistance in urinary outflow, and are useful in treating urinary tract obstruction due to benign prostatic obstruction or any diseases which relate directly or indirectly to dysfunction of urinary smooth muscle or its innervation.
Stimulation of central nervous system .alpha..sub.1 -adrenergic receptors suppresses appetite (Wellman, P.; Davies, B. Pharmacol. Biochem. Behav. 1991, 42, 97-100); thus, .alpha..sub.1 -adrenergic receptor antagonists are useful in treating anorexia.
The disclosures of these and other documents referred to throughout this application (e.g., in the Pharmacology section of the Detailed Description of the Invention) are incorporated herein by reference.